In order to gain a more complete understanding of the basic metabolic processes inherent in a normal or diseased cell, a genetic blueprint of the organism under study is necessary. Given the existence of several thousand genetic diseases in man, a genetic map facilitates gene discovery and is a necessary requirement for the assessment of gene structure and function. Once disease loci have been isolated and characterized and various aspects of their cell biology understood, then strategies for somatic gene therapy may be developed. This latter approach represents a therapeutic solution for previously untreatable conditions. Gene mapping in humans has proceeded at an accelerated pace over the past two decades due to a series of technical developments. Human-rodent cell hybrids, direct in situ chromosome hybridization, the discovery of highly polymorphic DNA markers, the establishment of three-generation reference families, and mathematical algorithms have all contributed enormously to the placement of over 10,000 genes and markers to the current human genetic map. The Genetics Section has been actively involved for a number of years in an international collaborative gene mapping effort by utilizing all of the above described technologies. Some of the genes that have been mapped recently include a novel protein disulfide isomerase, several signal transducers and activators of transcription (Stat loci), an actin bundling protein, various interleukins and other immunological cytokines, and gene that are differentially expressed in human tumors. The principal investigator is represented in the human genome projects as an elected member of the Human Genome Organization (HUGO) and is chairman o the International Committee of Comparative Gene Mapping.